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Tolerance to the effects of physostigmine and oxotremorine in rats was evaluated using a multiple fixed-ratio 10, extinction schedule of food presentation. Physostigmine was administered either once daily or three times daily for 18 consecutive days. Tolerance to physostigmine's response decreasing effects was observed under both administration regimens. Cumulative dose-effect functions for oxotremorine (0.0056-0.562 mg/kg) were determined before and after chronic physostigmine administration. Oxotremorine's potency to produce response rate suppression decreased in rats receiving physostigmine three times daily but did not substantially change in rats receiving single daily injections. These results demonstrate that the dose or duration of action of physostigmine can determine whether tolerance to physostigmine's effects is accompanied by cross-tolerance to oxotremorine's effects.
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